The statements in this section merely provide background information related to the present disclosure and may not constitute prior art.
Mucins are a family of secreted and cell-surface glycoproteins expressed by most epithelial tissues. Mucins are directed to the surface of epithelial tissues and are thought to play a protective role. Alterations in mucin proteins have been noted in conditions such as gastritis and peptic ulcer disease, Crohn's disease, ulcerative colitis, and intestinal cancers. Mucins can be grouped into two categories, secreted mucin proteins or membrane-bound mucin proteins. Secreted mucins are characterized by carboxyl- and amino-terminal domains termed “Von Willebrand-type D” domains that flank a large serine and threonine-rich domain that is heavily glycosylated. These mucins are able to join end-to-end to form long polymers that are highly viscous in solution. Membrane-bound mucins are characterized by a carboxyl-terminal domain containing a small cytoplasmic domain, a hydrophobic membrane-spanning domain, and an extracellular domain that is characterized in some cases by a cysteine-rich domain and a large serine- and threonine-rich glycosylated domain. Messenger RNA splice variants of these genes have been described that encode proteins without the membrane-spanning domain, which allows them to function as a secreted monomeric mucin. In this regard the membrane-spanning mucins can be considered bi-functional, existing as both membrane-associated proteins and as secreted proteins.
The etiology of IBD is not well understood. However, pre-clinical data in rodent models of IBD indicate that treatment with E. coli-derived mucins (Mouse Muc3 proteins) prevents and reverses the ulcerations of the colonic wall and decreases the accompanying chronic symptoms of diarrhea and body weight loss.
IBD is prevalent in the United States and Western Europe and currently estimated to afflict 1.2 million people in the United States with approximately 30,000 new cases diagnosed each year. Worldwide, it is estimated that 4 million people suffer from IBD. In addition, IBD has been associated with an increased risk of colorectal cancer. To date there are no approved medications to treat IBD that act by restoring the epithelial layer of the intestine or colon. Currently there is no known cure for IBD and existing drug therapies are only utilized to suppress symptoms. In addition, current therapies are associated with significant toxicities.
Ulcerative colitis is a common form of IBD. Ulcerative colitis is generally recognized as an immune-mediated disorder resulting from an abnormal interaction between colonic microflora and mucosal immune cells in a genetically susceptible host. The nature of the mucosal immune abnormality remains unclear, and how this interaction develops is not well understood. In addition, all drugs currently on the market for the treatment of ulcerative colitis have side effects and none of them can cure the disease. Oral mucositis is a condition that occurs in cancer patients treated for head and neck cancer with chemotherapy or radiation and has no accepted therapy
The current treatments for IBD are often only partially effective and have numerous toxicities. Thus, there is a need for additional treatment compositions and modalities to treat IBD and related colitides that are safe and do not induce cellular proliferation or increase the risk of tumorgenesis.